Document Detail


Mast cell chymase and tryptase as targets for cardiovascular and metabolic diseases.
MedLine Citation:
PMID:  23016684     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mast cells are critical effectors in inflammatory diseases, including cardiovascular and metabolic diseases and their associated complications. These cells exert their physiological and pathological activities by releasing granules containing histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Several recent human and animal studies have shown direct or indirect participation of mast cell-specific proteases in atherosclerosis, abdominal aortic aneurysms, obesity, diabetes, and their complications. Animal studies have demonstrated the beneficial effects of highly selective and potent chymase and tryptase inhibitors in several experimental cardiovascular and metabolic diseases. In this review, we summarize recent discoveries from in vitro cell-based studies to experimental animal disease models, from protease knockout mice to treatments with recently developed selective and potent protease inhibitors, and from patients with preclinical disorders to those affected by complications. We hypothesize that inhibition of chymases and tryptases would benefit patients suffering from cardiovascular and metabolic diseases.
Authors:
Aina He; Guo-Ping Shi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current pharmaceutical design     Volume:  19     ISSN:  1873-4286     ISO Abbreviation:  Curr. Pharm. Des.     Publication Date:  2013  
Date Detail:
Created Date:  2013-02-08     Completed Date:  2013-07-30     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1114-25     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiovascular Diseases / drug therapy*,  enzymology
Chymases / antagonists & inhibitors*
Enzyme Inhibitors / therapeutic use*
Humans
Mast Cells / enzymology*
Metabolic Diseases / drug therapy*,  enzymology
Mice
Tryptases / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
HL60942/HL/NHLBI NIH HHS; HL81090/HL/NHLBI NIH HHS; HL88547/HL/NHLBI NIH HHS; R01 HL060942/HL/NHLBI NIH HHS; R01 HL081090/HL/NHLBI NIH HHS; R01 HL088547/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; EC 3.4.21.39/Chymases; EC 3.4.21.59/Tryptases
Comments/Corrections

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